Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Haemoglobin F has been isolated from the red cells of individuals with the Greek form of hereditary persistence of fetal haemoglobin (HPFH), and the glycine/alanine composition of the gamma CB3 peptides determined. In contrast to previous reports we have shown that the Hb F of the Greek HPFH heterozygotes contains significant amounts of G gamma chains and circumstantial evidence indicates that these are the products of the same chromosome that carries the Greek HPFH determinant. Hence this chromosome must be directing the synthesis of G gamma, A gamma and (probably) beta and delta chains, thus implying that the Greek form of HPFH does not result from a deletion involving the globin chain structural genes. Analysis of the levels and structure of Hb F from the Greek HPFH heterozygotes and from separated cell populations from the Greek HPFH/beta thalassaemia compound heterozygotes indicate that the Greek HPFH determinant, while allowing an overall increase in gamma chain synthesis, is not the sole factor determining the absolute amount of Hb F production on a cellular basis.
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PMID:Occurrence of G gamma Hb F in Greek HPFH: analysis of heterozygotes and compound heterozygotes with beta thalassaemia. 9 88

The heterogeneity of residue 136 of the gamma-chain of human hemoglobin has been determined for a patient afflicted with severe alpha-thalassemia. Separation of the cord blood sample into the various constituent hemoglobins A, F, FI and Bart's were done on a column packed with DEAE Sephadex. The amount of glycine or alanine at position 136 was determined for hemoglobins F, FI and Bart's. The ratios determined for all three hemoglobins indicated that the G gamma/A gamma ratio is the same for all three fractions and is similar to that observed in normal cord blood samples.
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PMID:Heterogeneity of fetal hemoglobin in severe alpha-thalassemia. 48 8

The biosynthesis of two types of human fetal hemoglobin (Hb F), namely Hb F with G gamma chains having glycine in position 136 and Hb F with A gamma chains having alanine in position 136, was studied in blood samples and in cultures of erythroid precursors from blood of patients with different hemoglobinopathies. High pressure liquid chromatography (HPLC) was adapted to allow the separation of the methionyl-containing tryptic peptides G gamma T-15 and A gamma T-15 (which include the Gly leads to Ala polymorphism at position 136) from a digest of microquantitites of 35S-methionyl labelled Hb F. This method was sensitive enough to quantitate the relative production of the G ygamma and A gamma chains by erythroid colonies derived from cloned Burst Forming Units (bfu-e) which were cultured for 16 days on methylcellulose. The production of Hb F in these colonies was generally higher than the level of Hb F in blood except for subjects with the G gamma A gamma-HPFH heterozygosity. The G gamma to A gamma ratio in the Nb F produced in cultures of cells from G gamma delta beta-thalassemia or G gamma-HPFH heterozygotes was lower and that from A gamma-HPFH heterosygotes was higher than the ratios in the Hb F of the corresponding peripheral blood cells. Mixtures of G gamma and A gamma chains were present in cell cultures of SS patients, beta+-thalassemia homozygotes and G gamma A gamma-HPFH heterozygotes in a ratio similar to that in the Hb F of mature red cells. These data suggest that erythroblasts in BFU-E derived colonies reactivate all available gamma chain structural genes, both in cis and in trans to the abnormal determinant. Hb F biosynthesis by adult blood samples concerns primarily the G gamma chains. This was particularly striking for blood samples in which erythroblasts were absent and the biosynthesis took place in fetal reticulocytes. Thus, the F-retuculocytes in blood of A gamma-HPFH heterozygotes with about 5% Hb F of the A gamma type produced primarily Hb F with G gamma chains. Similar differences were observed for G gamma A gamma-HPFH heterozygotes and, less strinkingly, for SS patients. A satisfactory explanation for this observation has not yet been obtained.
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PMID:The synthesis of fetal hemoglobin types in red blood cells and in BFU-E derived colonies from peripheral blood of patients with sickle cell anemia, beta+ - and delta beta-thalassemia, various forms of hereditary persistence of fetal hemoglobin, normal adults and newborn. 50 Mar 69

We have studied a Portuguese family with a dominant beta-thalassaemia trait that was present in one member of each of three generations. It was characterized by a moderate anaemia, microcytosis and hypochromia, anisopoikilocytosis, Heinz body formation in peripheral red cells, splenomegaly, and a blood transfusion requirement during pregnancy. Sequence analyses of amplified DNA detected a deletion of (G) TG.GCT.GGT.GT(G) at codons 134-137 (Val.Ala.Gly.Val) and the insertion of (G)GC.AG(G) (Gly.Arg) at the same location. Thus, the resulting beta chain has an abnormal structure only at codons 134-137 and is two residues shorter than the normal 146 residues. This chain could not be detected in circulating red cells and must be degraded rapidly by proteolysis because the Heinz bodies consisted mainly of alpha chains.
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PMID:Dominant beta-thalassaemia trait in a Portuguese family is caused by a deletion of (G)TGGCTGGTGT(G) and an insertion of (G)GCAG(G) in codons 134, 135, 136 and 137 of the beta-globin gene. 165 62

The molecular basis of most beta-thalassemia syndromes has been defined, while the spectrum of mutations causing delta-thalassemia is not well characterized. In an attempt to identify such mutations, the region encompassing the delta-globin gene from three Greek Cypriot families suspected of having delta-thalassemia was amplified by polymerase chain reaction (PCR), and DNA sequence determined using an automated fluorescence-based sequencer. Four novel mutations were identified: a G----T change at codon 27 that results in an alanine to serine change; a C----T change at codon 116 converting arginine to cysteine; a T----C change at codon 141 converting leucine to proline; and an AG----GG change at the consensus 3'-acceptor site in IVS-2. While the latter is clearly a thalassemic mutation, the low hemoglobin A2 in the first three may be due to either decreased production or instability of the altered delta-globin chain. All four mutations may be detected by PCR amplification of genomic DNA followed by restriction enzyme digestion. Two mutations abolish restriction sites while two create new cleavage sites. Screening for molecular defects that cause delta-thalassemia or unstable delta-globin by PCR amplification and restriction enzyme digestion will lead to correct diagnosis of beta/delta-thalassemia compound heterozygotes and improved genetic counseling.
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PMID:Identification of four novel delta-globin gene mutations in Greek Cypriots using polymerase chain reaction and automated fluorescence-based DNA sequence analysis. 174 90

Hb Stanmore is a new hemoglobin variant with the amino acid substitution beta 111(G13)Val----Ala. It is unstable and has a low oxygen affinity. The propositus (of Italian nationality) is a double-heterozygote for Hb Stanmore and beta(0)-thalassemia.
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PMID:A new unstable and low oxygen affinity hemoglobin variant: Hb Stanmore [beta 111(G13)Val----Ala]. 191 37

A severe hemolytic anemia with microcytosis and hypochromia was present in a young adopted Indian patient. Reversed phase high performance liquid chromatographic methodology and heat stability tests detected an unstable alpha chain which was present in 3 to 5% of the total hemoglobin. A larger quantity of the alpha X chain was obtained by preparative reversed phase high performance liquid chromatography. Structural analyses identified an Ala----Pro replacement at position 130 of the alpha chain. The instability of the variant, named Hb Sun Prairie, is comparable to that of Hb Bibba [alpha 136 (H19)Leu----Pro]. Gene mapping failed to detect an alpha-thalassemia deletion (alpha alpha/alpha alpha), while dot-blot analysis of amplified DNA with synthetic probes localized a G----C mutation in codon 130 (resulting in the Ala----Pro mutation) of the alpha 2-globin genes of both chromosomes. These results suggest a homozygosity for the G----C mutation and the condition alpha 2(G----C)alpha 1/alpha 2(G----C)alpha 1 adequately explains the rather severe clinical status of this child, including the marked microcytosis and hypochromia. Unfortunately, family studies to exclude the presence of a large deletion involving all zeta- and alpha-globin genes were not possible.
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PMID:Hb Sun Prairie or alpha(2)130(H13)Ala----Pro beta 2, a new unstable variant occurring in low quantities. 207 31

Seropositivity to HBV (HBsAg) in multi-transfused patients of haemophilia A, haemophilia B, B thalassaemia and EB thalassaemia from Eastern India, was found to be 9, 0, 22.1 and 13 per cent respectively. HIV seropositivity was detected in patients of haemophilia A (4.4%) and B thalassaemia (0.8%) who received plasma components and packed cells periodically. Seropositivity to both HBsAg and HIV was found in one patient of haemophilia A. Serum alanine amino transferase (ALT), raised in multi-transfused thalassaemics suggests concurrent hepatitis which might have enhanced the transmission of viruses due to disturbed immune status. The universal voluntary blood donation programme, screening of blood for HBV and HIV by sensitive tests, early immunisation and periodic monitoring of HBV and HIV status are prerequisites for the management of transfusion dependent thalassaemia and haemophilia.
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PMID:HBV & HIV seropositivity in multi-transfused haemophilics & thalassaemics in eastern India. 234 33

We have studied a few members of two Turkish families, who had a beta-thalassemia of the intermediate type. An abnormal hemoglobin was found in both families, which when present in association with beta(0)-thalassemia was considered to be the primary cause for the increased severity of the disease. In the first family this variant was Hb Knossos [beta 27(B9)Ala----Ser] which occurred together with the frameshift in codon #8 type of beta(0)-thalassemia. This compound heterozygosity, observed for the first time in the Turkish population was characterized by a considerable increase in Hb F production, mainly of the G gamma type, as expected for a chromosome with haplotype IV. In the second family, the variant was Hb City of Hope [beta 69(E13)Gly----Ser] which was present in combination with an unknown type of beta-thalassemia. The increase in Hb F production in the compound heterozygote was minimal. Reversed phase high performance liquid chromatography and the DNA amplification-synthetic oligonucleotide probe procedure were major tools in identifying the different abnormalities.
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PMID:Beta-thalassemia intermedia in two Turkish families is caused by the interaction of Hb Knossos [beta 27(B9)Ala----Ser] and of Hb City of Hope [beta 69(E13)Gly----ser] with beta (0)-thalassemia. 246 92

Detailed data are presented concerning the relative amounts of Hb A and two alpha chain variants (Hb Duan with alpha 75 Asp----Ala, and Hb Westmead with alpha 122 His----Gln), and the occurrence of an alpha-thalassemia-2 heterozygosity in five members of a small Chinese family. The three children who have the three abnormalities inherited the alpha-Duan and alpha-thalassemia-2 heterozygosities from their father, and the alpha-Westmead heterozygosity from their mother. The base substitution which leads to the synthesis of the alpha-Duan chain occurred at codon 75 of the alpha 1 globin gene of the chromosome which also carried the alpha-thalassemia-2 deletion; the concentration of alpha-Duan (37% of total alpha) is similar to that observed for other alpha chain variants, linked to an alpha-thalassemia-2 condition.
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PMID:Hb Duan [alpha 75(EF4)Asp----Ala], Hb Westmead [alpha 122(H5)His----Gln], and alpha-thalassemia-2 (-4.2 Kb deletion) in a Chinese family. 338 94


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